The aim of this study was to determine whether a ketogenic diet could decrease nitrogen losses in cachectic cancer patients and at the same time reduce the supply of glucose for tumor energy metabolism. Five patients with malignant disease and severe weight loss (mean 32%) were fed via a fine bore nasogastric tube. A normal diet was given for 6 d and this was followed by 7 d of an isonitrogenous, isocaloric, ketogenic diet. Both diets were well tolerated. At 7 d the mean ketone body concentration in the blood of patients fed the ketogenic diet was 1.21 +/- 0.33 mM. This ketosis was associated with a significant reduction of the concentration in blood of glucose, lactate, and pyruvate (p less than 0.05). There was, however, no significant alteration in host N balance or whole-body protein synthesis, degradation, or turnover rates. Whether the change from glucose- to fat-derived energy substrates might reduce tumor growth rates in the long term remains to be determined.